Adipose-Derived Biogenic Nanoparticles for Suppression of Inflammation.

Extracellular vesicles secreted from adipose-derived mesenchymal stem cells (ADSCs) have therapeutic effects in inflammatory diseases. However, production of extracellular vesicles (EVs) from ADSCs is costly, inefficient, and time consuming. The anti-inflammatory properties of adipose tissue-derived EVs and other biogenic nanoparticles have not been explored. In this study, biogenic nanoparticles are obtained directly from lipoaspirate, an easily accessible and abundant source of biological material. Compared to ADSC-EVs, lipoaspirate nanoparticles (Lipo-NPs) take less time to process (hours compared to months) and cost less to produce (clinical-grade cell culture facilities are not required). The physicochemical characteristics and anti-inflammatory properties of Lipo-NPs are evaluated and compared to those of patient-matched ADSC-EVs. Moreover, guanabenz loading in Lipo-NPs is evaluated for enhanced anti-inflammatory effects. Apolipoprotein E and glycerolipids are enriched in Lipo-NPs compared to ADSC-EVs. Additionally, the uptake of Lipo-NPs in hepatocytes and macrophages is higher. Lipo-NPs and ADSC-EVs have comparable protective and anti-inflammatory effects. Specifically, Lipo-NPs reduce toll-like receptor 4-induced secretion of inflammatory cytokines in macrophages. Guanabenz-loaded Lipo-NPs further suppress inflammatory pathways, suggesting that this combination therapy can have promising applications for inflammatory diseases.

[1]  Q. Yuan,et al.  Extracellular vesicles from human adipose derived stem cells for the improvement of angiogenesis and fat grafting application. , 2019, Plastic and reconstructive surgery.

[2]  J. Wolfram,et al.  Extracellular vesicle-based drug delivery systems for cancer treatment , 2019, Theranostics.

[3]  J. Wolfram,et al.  Adipose-derived cellular and cell-derived regenerative therapies in dermatology and aesthetic rejuvenation , 2019, Ageing Research Reviews.

[4]  K. Rezvani,et al.  Mesenchymal stem cell-derived exosomes for clinical use , 2019, Bone Marrow Transplantation.

[5]  Chao Han,et al.  Pretreatment with Salvia miltiorrhiza Polysaccharides Protects from Lipopolysaccharides/d-Galactosamine-Induced Liver Injury in Mice through Inhibiting TLR4/MyD88 Signaling Pathway. , 2019, Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.

[6]  G. Evans,et al.  Adipose-derived stem cell extracellular vesicles: A systematic review✰. , 2019, Journal of plastic, reconstructive & aesthetic surgery : JPRAS.

[7]  H. Chou,et al.  Maternal inflammation exacerbates neonatal hyperoxia-induced kidney injury in rat offspring , 2019, Pediatric Research.

[8]  Hong Tang,et al.  Apolipoprotein A5 alleviates LPS/d-GalN-induced fulminant liver failure in mice by inhibiting TLR4-mediated NF-κB pathway , 2019, Journal of Translational Medicine.

[9]  J. Wolfram,et al.  Organotropic drug delivery: Synthetic nanoparticles and extracellular vesicles , 2019, Biomedical Microdevices.

[10]  James E. Tomkins,et al.  Secretome of adipose-derived mesenchymal stem cells promotes skeletal muscle regeneration through synergistic action of extracellular vesicle cargo and soluble proteins , 2019, Stem Cell Research & Therapy.

[11]  Mauro Ferrari,et al.  Clinical Cancer Nanomedicine. , 2019, Nano today.

[12]  Yueqiao Xu,et al.  Exosomes from adipose-derived mesenchymal stem cells prevent cardiomyocyte apoptosis induced by oxidative stress , 2019, Cell Death Discovery.

[13]  Y. Takakura,et al.  Preservation of exosomes at room temperature using lyophilization , 2018, International journal of pharmaceutics.

[14]  D. Dickson,et al.  Tangential Flow Filtration for Highly Efficient Concentration of Extracellular Vesicles from Large Volumes of Fluid , 2018, Cells.

[15]  Jing Xu,et al.  Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines , 2018, Journal of Extracellular Vesicles.

[16]  J. Merola,et al.  TNF Inhibitor-Induced Psoriasis: Proposed Algorithm for Treatment and Management , 2018, Journal of psoriasis and psoriatic arthritis.

[17]  M. Ferrari,et al.  Chloroquine and nanoparticle drug delivery: A promising combination , 2018, Pharmacology & therapeutics.

[18]  B. Péault,et al.  Higher Pericyte Content and Secretory Activity of Microfragmented Human Adipose Tissue Compared to Enzymatically Derived Stromal Vascular Fraction , 2018, Stem cells translational medicine.

[19]  C. Scarlett,et al.  Lipidomic profiling of extracellular vesicles derived from prostate and prostate cancer cell lines , 2018, Lipids in Health and Disease.

[20]  J. Dai,et al.  Pro inflammatory stimuli enhance the immunosuppressive functions of adipose mesenchymal stem cells-derived exosomes , 2018, Scientific Reports.

[21]  S. Kristensen,et al.  Investigation of procoagulant activity in extracellular vesicles isolated by differential ultracentrifugation , 2018, Journal of extracellular vesicles.

[22]  J. Wolfram,et al.  Extracellular vesicle therapeutics for liver disease , 2018, Journal of controlled release : official journal of the Controlled Release Society.

[23]  J. Lötvall,et al.  Detailed analysis of the plasma extracellular vesicle proteome after separation from lipoproteins , 2018, Cellular and Molecular Life Sciences.

[24]  William C Lamanna,et al.  Maintaining consistent quality and clinical performance of biopharmaceuticals , 2018, Expert opinion on biological therapy.

[25]  Dongfeng Guo,et al.  Exosomes from MiR-126-Overexpressing Adscs Are Therapeutic in Relieving Acute Myocardial Ischaemic Injury , 2017, Cellular Physiology and Biochemistry.

[26]  Lining Zhang,et al.  Exosomes From Adipose-Derived Stem Cells Attenuate Adipose Inflammation and Obesity Through Polarizing M2 Macrophages and Beiging in White Adipose Tissue , 2017, Diabetes.

[27]  M. Ferrari,et al.  A chloroquine-induced macrophage-preconditioning strategy for improved nanodelivery , 2017, Scientific Reports.

[28]  Mauro Ferrari,et al.  Contribution of Kupffer cells to liposome accumulation in the liver. , 2017, Colloids and surfaces. B, Biointerfaces.

[29]  Qing Xu,et al.  Human macrophages survive and adopt activated genotypes in living zebrafish , 2017, Scientific Reports.

[30]  M. Ferrari,et al.  Strategies for improving drug delivery: nanocarriers and microenvironmental priming , 2017, Expert opinion on drug delivery.

[31]  Y. Talmon,et al.  A direct-imaging cryo-EM study of shedding extracellular vesicles from leukemic monocytes. , 2017, Journal of structural biology.

[32]  Romaric Lacroix,et al.  Methodological Guidelines to Study Extracellular Vesicles. , 2017, Circulation research.

[33]  Mauro Ferrari,et al.  Taking the vehicle out of drug delivery. , 2017, Materials today.

[34]  E. Galanis,et al.  Clinical Trials with Oncolytic Measles Virus: Current Status and Future Prospects. , 2017, Current cancer drug targets.

[35]  M. Barbosa,et al.  Extracellular Vesicles: Immunomodulatory messengers in the context of tissue repair/regeneration , 2017, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[36]  Hongguang Zhang,et al.  hucMSC Exosome-Derived GPX1 Is Required for the Recovery of Hepatic Oxidant Injury. , 2017, Molecular therapy : the journal of the American Society of Gene Therapy.

[37]  R. Cancedda,et al.  Mesenchymal Stem Cell‐Derived Extracellular Vesicles as Mediators of Anti‐Inflammatory Effects: Endorsement of Macrophage Polarization , 2017, Stem cells translational medicine.

[38]  M. Ferrari,et al.  Enzyme-responsive multistage vector for drug delivery to tumor tissue. , 2016, Pharmacological research.

[39]  Parvin Akbarzadehlaleh,et al.  Mesenchymal Stem Cell-Derived Exosomes: New Opportunity in Cell-Free Therapy. , 2016, Advanced pharmaceutical bulletin.

[40]  M. Ferrari,et al.  Hesperetin Liposomes for Cancer Therapy. , 2016, Current drug delivery.

[41]  C. Ventura,et al.  Adipose Tissue and Mesenchymal Stem Cells: State of the Art and Lipogems® Technology Development , 2016, Current Stem Cell Reports.

[42]  A. Sudo,et al.  Guanabenz Downregulates Inflammatory Responses via eIF2α Dependent and Independent Signaling , 2016, International journal of molecular sciences.

[43]  K. Sakthivel,et al.  Acacia ferruginea inhibits inflammation by regulating inflammatory iNOS and COX-2 , 2016, Journal of immunotoxicology.

[44]  A. Hill,et al.  Techniques used for the isolation and characterization of extracellular vesicles: results of a worldwide survey , 2016, Journal of extracellular vesicles.

[45]  Heikki Saari,et al.  Microvesicle- and exosome-mediated drug delivery enhances the cytotoxicity of Paclitaxel in autologous prostate cancer cells. , 2015, Journal of controlled release : official journal of the Controlled Release Society.

[46]  Z. Giricz,et al.  Isolation of Exosomes from Blood Plasma: Qualitative and Quantitative Comparison of Ultracentrifugation and Size Exclusion Chromatography Methods , 2015, PloS one.

[47]  Mauro Ferrari,et al.  Safety of Nanoparticles in Medicine. , 2015, Current drug targets.

[48]  V. Govorun,et al.  Isolation of exosomes by differential centrifugation: Theoretical analysis of a commonly used protocol , 2015, Scientific Reports.

[49]  S. Lim,et al.  Mesenchymal stem cell exosomes. , 2015, Seminars in cell & developmental biology.

[50]  Go-woon Kim,et al.  IL-6 inhibitors for treatment of rheumatoid arthritis: past, present, and future , 2015, Archives of pharmacal research.

[51]  Shaowu Cheng,et al.  HDL and cognition in neurodegenerative disorders , 2014, Neurobiology of Disease.

[52]  Verónica Álvarez,et al.  Immunomodulatory Potential of Human Adipose Mesenchymal Stem Cells Derived Exosomes on in vitro Stimulated T Cells , 2014, Front. Immunol..

[53]  Toshio Tanaka,et al.  IL-6 in inflammation, immunity, and disease. , 2014, Cold Spring Harbor perspectives in biology.

[54]  J. Schageman,et al.  Analysis of the RNA content of the exosomes derived from blood serum and urine and its potential as biomarkers , 2014, Philosophical Transactions of the Royal Society B: Biological Sciences.

[55]  Hemlata,et al.  Adverse events related to blood transfusion , 2014, Indian journal of anaesthesia.

[56]  M. Ferrari,et al.  Evaluation of anticancer activity of celastrol liposomes in prostate cancer cells , 2014, Journal of microencapsulation.

[57]  E. Yoon,et al.  Immunosuppressive activity of adipose tissue-derived mesenchymal stem cells in a rat model of hind limb allotransplantation. , 2014, Transplantation proceedings.

[58]  B. Yu,et al.  Exosomes Derived from Mesenchymal Stem Cells , 2014, International journal of molecular sciences.

[59]  R. Nieuwland,et al.  Single-step isolation of extracellular vesicles by size-exclusion chromatography , 2014, Journal of extracellular vesicles.

[60]  R. Pink,et al.  Routes and mechanisms of extracellular vesicle uptake , 2014, Journal of extracellular vesicles.

[61]  K. Braeckmans,et al.  Electroporation-induced siRNA precipitation obscures the efficiency of siRNA loading into extracellular vesicles. , 2013, Journal of controlled release : official journal of the Controlled Release Society.

[62]  Giuseppe Battaglia,et al.  Exploiting endocytosis for nanomedicines. , 2013, Cold Spring Harbor perspectives in biology.

[63]  Winston Patrick Kuo,et al.  Current methods for the isolation of extracellular vesicles , 2013, Biological chemistry.

[64]  G. Teng,et al.  Let-7b Is Involved in the Inflammation and Immune Responses Associated with Helicobacter pylori Infection by Targeting Toll-Like Receptor 4 , 2013, PloS one.

[65]  G. Camussi,et al.  Role of stem-cell-derived microvesicles in the paracrine action of stem cells. , 2013, Biochemical Society transactions.

[66]  Lynne T. Bemis,et al.  Standardization of sample collection, isolation and analysis methods in extracellular vesicle research , 2013, Journal of extracellular vesicles.

[67]  K. Wilhelmsen,et al.  Alveolar Macrophages and Toll-like Receptor 4 Mediate Ventilated Lung Ischemia Reperfusion Injury in Mice , 2012, Anesthesiology.

[68]  Y. Barenholz.  Doxil®--the first FDA-approved nano-drug: lessons learned. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[69]  M. Masserini,et al.  Cellular uptake of coumarin-6 as a model drug loaded in solid lipid nanoparticles. , 2011, Journal of physiology and pharmacology : an official journal of the Polish Physiological Society.

[70]  K. Vickers,et al.  MicroRNAs are Transported in Plasma and Delivered to Recipient Cells by High-Density Lipoproteins , 2011, Nature Cell Biology.

[71]  D. Stumpo,et al.  Inflammation: cytokines and RNA‐based regulation , 2010, Wiley interdisciplinary reviews. RNA.

[72]  M. Casiraghi,et al.  Novel critical role of Toll-like receptor 4 in lung ischemia-reperfusion injury and edema. , 2009, American journal of physiology. Lung cellular and molecular physiology.

[73]  A. Shimamoto,et al.  Toll-like receptor 4 mediates lung ischemia-reperfusion injury. , 2006, The Annals of thoracic surgery.

[74]  J Bruce German,et al.  Lipoproteins: When size really matters. , 2006, Current opinion in colloid & interface science.

[75]  M. Hochberg.  COX-2 selective inhibitors in the treatment of arthritis: a rheumatologist perspective. , 2005, Current topics in medicinal chemistry.

[76]  A. Gotto,et al.  Functional Interplay Between the Macrophage Scavenger Receptor Class B Type I and Pitavastatin (NK-104) , 2004, Circulation.

[77]  A. Tall,et al.  High Density Lipoprotein (HDL) Particle Uptake Mediated by Scavenger Receptor Class B Type 1 Results in Selective Sorting of HDL Cholesterol from Protein and Polarized Cholesterol Secretion* , 2001, The Journal of Biological Chemistry.

[78]  F. Kronenberg,et al.  Effect of sample storage on the measurement of lipoprotein[a], apolipoproteins B and A-IV, total and high density lipoprotein cholesterol and triglycerides. , 1994, Journal of lipid research.

[79]  R P Carlson,et al.  The antiinflammatory action of guanabenz is mediated through 5-lipoxygenase and cyclooxygenase inhibition. , 1987, European journal of pharmacology.

[80]  R. N. Brogden,et al.  Guanabenz , 1983, Drugs.

[81]  S. Jay,et al.  Preservation and Storage Stability of Extracellular Vesicles for Therapeutic Applications , 2017, The AAPS Journal.

[82]  B. De Geest,et al.  Therapeutic potential of HDL in cardioprotection and tissue repair. , 2015, Handbook of experimental pharmacology.

[83]  M. Carafa,et al.  Liposomal chemotherapeutics. , 2013, Future oncology.

[84]  J. Joh,et al.  Enhancement of the immunosuppressive effect of human adipose tissue-derived mesenchymal stromal cells through HLA-G1 expression. , 2012, Cytotherapy.

[85]  M. Federspiel,et al.  Manufacture of measles viruses. , 2011, Methods in molecular biology.

[86]  Jun-Ming Zhang,et al.  Cytokines, Inflammation, and Pain , 2007, International anesthesiology clinics.

[87]  D. Prockop,et al.  Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. , 2006, Cytotherapy.